On the accuracy factors and computational cost of the GIAO-DFT calculation of N NMR chemical shifts of amides.

The main factors affecting the accuracy and computational cost of Gauge-independent Atomic Orbital-density functional theory (GIAO-DFT) calculation of N NMR chemical shifts in the benchmark series of 16 amides are considered. Among those are the choice of the DFT functional and basis set, solvent effects, internal reference conversion factor and applicability of the locally dense basis set (LDBS) scheme. Solvent effects are treated within the polarizable continuum model (PCM) scheme as well as at supermolecular level with solvent molecules considered in explicit way. The best result is found for Keal and Tozer's KT3 functional used in combination with Jensen's pcS-3 basis set with taking into account solvent effects within the polarizable continuum model. The proposed LDBS scheme implies pcS-3 on nitrogen and pc-2 elsewhere in the molecule. The resulting mean average error for the calculated N NMR chemical shifts is about 6 ppm. The application of the LDBS approach tested in a series of 16 amides results in a dramatic decrease in computational cost (more than an order of magnitude in time scale) with insignificant loss of accuracy.